Pediatric high-impact conditions in the United States: retrospective analysis of hospitalizations and associated resource use

ABSTRACT: BACKGROUND: Child mortality in the United States has decreased over time, with advance in biomedicine. Little is known about patterns of current pediatric health care delivery for children with the leading causes of child death (high-impact conditions). We described patient and hospital characteristics, and hospital resource use, among children hospitalized with high-impact conditions, according to illness severity. METHODS: We conducted a retrospective study of children 0-18 years of age, hospitalized with discharge diagnoses of the ten leading causes of child death, excluding diagnoses not amenable to hospital care, using the 2006 version of the Kid's Inpatient Database. National estimates of average and cumulative hospital length of stay and total charges were compared between types of hospitals according to patient illness severity, which was measured using all-patient refined diagnosis related group severity classification into minor-moderate, major, and extreme severity. RESULTS: There were an estimated 3,084,548 child hospitalizations nationally for high-impact conditions in 2006, distributed evenly among hospital types. Most (84.4%) had minormoderate illness severity, 12.2% major severity, and 3.4% were extremely ill. Most (64%) of the extremely ill were hospitalized at children's hospitals. Mean hospital stay was longest among the extremely ill (32.8 days), compared with major (9.8 days, p < 0.0001), or minormoderate (3.4 days, p < 0.001) illness severity. Mean total hospital charges for the extremely ill were also significantly higher than for hospitalizations with major or minor-moderate severity. Among the extremely ill, more frequent hospitalization at children's hospitals resulted in higher annual cumulative charges among children's hospitals ($ 7.4 billion), compared with non-children teaching hospitals ($ 3.2 billion, p = 0.023), and non-children's non-teaching hospitals ($ 1.5 billion, p < 0.001). Cumulative annual length of hospital stay followed the same pattern, according to hospital type. CONCLUSION: Gradation of increasing illness severity among children hospitalized for high-impact conditions was associated with concomitantly increased resource consumption. These findings have significant implications for children's hospitals which appear to accrue the highest resource use burden due to preferential hospitalization of the most severely ill at these hospitals.     

Bacteriologic and clinical efficacy of oral gatifloxacin for the treatment of recurrent/nonresponsive acute otitis media: an open label, noncomparative, double tympanocentesis study

BACKGROUND: Gatifloxacin is an 8-methoxyfluoroquinolone with good activity against respiratory pathogens. OBJECTIVES: To document the bacteriologic and clinical efficacy of gatifloxacin in recurrent/nonresponsive acute otitis media (AOM). METHODS: One hundred sixty patients 6 to 48 months of age with recurrent/nonresponsive AOM received gatifloxacin suspension (10 mg/kg once daily for 10 days). Recurrent AOM was defined as > or =3 AOM episodes during the previous 6 months or > or =4 AOM episodes during the previous 12 months. Nonresponsive AOM was defined as AOM occurring < or =14 days after completing antibiotic treatment or not improving after > or =48 h of therapy. Middle ear fluid (MEF) obtained by tympanocentesis pretreatment (Day 1) and 3 to 5 days after initiation of treatment (Days 4 to 6) was cultured. Additional MEF cultures were obtained if clinical failure or recurrence of AOM occurred. Bacteriologic failure was defined by culture-positive MEF during treatment. Patients were followed until Days 22 to 28. Susceptibility was determined by broth microdilution. RESULTS: One hundred twenty-eight (80%) patients completed treatment, and 32 discontinued the study prematurely (adverse events, 17; lost to follow-up, 10; consent withdrawal, 3; and laboratory abnormalities, 2). From 89 patients (median age, 1 year; median number of prior AOM episodes, 4; range, 0 to 12), 121 pathogens were recovered: Haemophilus influenzae, 74 (61%); Streptococcus pneumoniae, 36 (30%); Moraxella catarrhalis, 9 (7%); and Streptococcus pyogenes, 2 (2%). The 36 S. pneumoniae isolates were susceptible to gatifloxacin (MIC50 0.25 microg/ml); 26 of 36 (72%) were penicillin-nonsusceptible (15 fully resistant). All 74 H. influenzae isolates were susceptible to gatifloxacin (MIC < or = 0.03 mg/ml). Fourteen of 74 (19%) and 9 of 9 (100%) H. influenzae and M. catarrhalis isolates, respectively, produced beta-lactamase. Bacteriologic eradication was achieved for 118 of 121 (98%) pathogens: 74 of 74 H. influenzae; 34 of 36 (94%) S. pneumoniae; 9 of 9 M. catarrhalis; and 1 of 2 S. pyogenes. Clinical improvement/cure at end of treatment was seen in 103 of 114 (90%) clinically evaluable patients. Clinical recurrence of AOM after completion of therapy occurred in 31 patients. Of the 27 recurrent AOM cases in which tympanocentesis was performed, there were 16 (59%) new infections, 4 (15%) culture-negative results and only 7 (26%) true bacteriologic relapses. Adverse events were recorded in 21 of 160 (13%) patients: vomiting, 16; diarrhea, 3; maculopapular rash, 2. No articular adverse events were recorded. CONCLUSION: Gatifloxacin is efficacious and safe for the treatment of recurrent/nonresponsive AOM.     

Superior relative efficacy of live attenuated influenza vaccine compared with inactivated influenza vaccine in young children with recurrent respiratory tract infections

BACKGROUND: Young children have a high incidence of influenza and influenza-related complications. This study compared the efficacy and safety of cold-adapted influenza vaccine, trivalent (CAIV-T) with trivalent inactivated influenza vaccine (TIV) in young children with a history of recurrent respiratory tract infections (RTIs). METHODS: Children 6 to 71 months of age were randomized to receive 2 doses of CAIV-T (n = 1101) or TIV (n = 1086), 35 +/- 7 days apart before the start of the 2002-2003 influenza season and were followed up for culture-confirmed influenza, effectiveness outcomes, reactogenicity, and adverse events. RESULTS: Overall, 52.7% (95% confidence interval [CI] = 21.6%-72.2%) fewer cases of influenza caused by virus strains antigenically similar to vaccine were observed in CAIV-T than in TIV recipients. Greater relative efficacy for CAIV-T was observed for the antigenically similar A/H1N1 (100.0%; 95% CI = 42.3%-100.0%) and B (68.0%; 95% CI = 37.3%-84.8%) strains but not for the antigenically similar A/H3N2 strains (-97.1%; 95% CI = -540.2% to 31.5%). Relative to TIV, CAIV-T reduced the number of RTI-related healthcare provider visits by 8.9% (90% CI = 1.5%-15.8%) and missed days of school, kindergarten, or day care by 16.2% (90% CI = 10.4%-21.6%). Rhinitis and rhinorrhea, otitis media, and decreased appetite were the only events that were reported more frequently in CAIV-T subjects. There was no difference between groups in the incidence of wheezing after vaccination. CONCLUSIONS: CAIV-T was well tolerated in these children with RTIs and demonstrated superior relative efficacy compared with TIV in preventing influenza illness.     

Henoch-Schonlein syndrome in northern Indian children.

In order to evaluate clinical features and renal pathological findings of Henoch-Schonlein syndrome (HSS) in northern Indian Children, we studied 47 such cases. The mean age at onset was 8.5 yr; sex ratio (M:F) 2.6:1. The clinical features were purpuric rash (96%), abdominal pain (64%), Henoch-Schonlein nephritis (51%) and arthralgias (47%). Patients younger than 6 yr also showed urticarial rash or edema of scalp and extremities. Henoch-Schonlein nephritis (HSN) and abdominal symptoms were more common in older cases. The manifestations of HSN were asymptomatic hematuria and/or proteinuria (n = 15), acute nephritic syndrome (n = 6), and nephrotic syndrome (n = 3). The severity of clinical manifestations correlated with the renal pathologic findings. On follow up, 29% cases showed renal impairment. The prognosis was poor in patients with the acute nephritic or nephrotic syndrome and crescents in more than 50% glomeruli. Combination of clinical data and renal biopsy findings are important in assessing the long-term outcome in cases with HSN.     

儿童2009甲型H1N1流感危重症14例临床特征

目的 分析儿童2009甲型H1N1流感危重症的临床特征.方法 对2009年10月1日至12月25日,我院儿科重症监护病房(PICU)14例2009甲型H1N1流感危重症患儿的临床特征及其预后进行分析.结果 14例平均年龄(4.91±4.14)岁,男女各7例,发病到入院时间为(3.09±1.30)d,从入院到入PICU时间为(0.95±0.96)d,所有患儿均表现出明显的低氧血症,入ICU时平均PaO2/FiO2(氧合指数)为(191.27±80.58)mm Hg(1 mm Hg=0.133 kPa),11例(78.6%)出现ARDS,10例(71.4%)行机械通气,平均通气时间为(12.51±10.03)d,平均ICU住院时间为(12.58±10.65)d,平均rRT-PCR检测甲型H1N1核酸呈阳性时间(17.27±5.57)d;8例(57.1%)患儿有缺铁性贫血、脑瘫和先天性心脏病等基础疾病;CK(肌酸激酶)、CK-MB(肌酸激酶同工酶)、cTnI(肌钙蛋白)和LDH(乳酸脱氢酶)在这些患儿中都有不同程度的升高;入院时第3代死亡危险评分(PRISM Ⅲ)较高和危重病例评分(PCIS)较低的患儿机械通气时间和ICU住院时间较长(P＜0.05).结论 苏州地区儿童2009甲型H1N1流感危重症病情进展快,短时间内即出现显著的低氧血症,甚至ARDS,并伴有不同程度的心肌损害,早期发现不利因素加以干预,是治疗成功的关键.     

The Immunization Monitoring Program Active (IMPACT) prospective five year study of Canadian children hospitalized for chickenpox or an associated complication

BACKGROUND: Varicella vaccine was approved for use in Canada in 1998. A major goal of universal varicella vaccine programs is to reduce severe infection and associated complications. Baseline data are essential against which to judge the effectiveness of routine childhood immunization. OBJECTIVE: To describe morbidity and mortality among children hospitalized for chickenpox. Methods. From January 1, 1991, to March 31, 1996, chickenpox admissions to 11 pediatric referral centers were actively identified. Patient and illness characteristics were compared for 3 subgroups defined by prior health: healthy; unhealthy but immunocompetent; immunocompromised. RESULTS: Of 861 cases 488 (56.7%) were healthy, 75(8.7%) were unhealthy and 298 (34.6%) were immunocompromised. The immunocompromised children differed from healthy/unhealthy cases in mean age (6.4 vs. 4.0/4.6 years, respectively, P < 0.0001); median interval from rash onset to admission (2 vs. 5/5 days, P < 0.0001); complication rate (20% vs. 90%/79%; P = 0.001); and rate of acyclovir therapy (98% vs. 24%/39%; P = 0.001). Unhealthy vs. healthy cases had a higher frequency (P < 0.01) of intensive care (13.3% vs. 4.7%), ventilation (9.3% vs. 2.0%) and death (4% vs. 0.2%). CONCLUSION: These data provide a baseline for morbidity/mortality resulting from chickenpox before varicella vaccine use in Canada.     

Prediction of resistance to intravenous immunoglobulin treatment in patients with Kawasaki disease

OBJECTIVES: The objective of this study was to find the predictors and generate a prediction score of resistance to intravenous immunoglobulin (IVIG) in patients with Kawasaki disease (KD). STUDY DESIGN: Patients diagnosed as having KD were sampled when they received initial high-dose IVIG treatment (2 g/kg dose) within 9 days of illness (n = 320). These patients were divided into 2 groups: the resistance (n = 41) and the responder (n = 279). The following data were obtained and compared between resistance and responder: age, sex, illness days at initial treatment, and laboratory data. RESULTS: Multivariate logistic regression analysis identified age, illness days, platelet count, alanine aminotransferase (ALT), and C-reactive protein (CRP) as significant predictors for resistance to IVIG. We generated prediction score assigning 1 point for (1) infants less than 6 months old, (2) before 4 days of illness, (3) platelet count or= 8 mg/dL, as well as 2 points for (5) ALT >or= 80 IU/L. Using a cut-off point of 3 and more with this prediction score, we could identify the IVIG-resistant group with 78% sensitivity and 76% specificity. CONCLUSIONS: Resistance to IVIG treatment can be predicted using age, illness days, platelet count, ALT, and CRP. Randomized, multicenter clinical trials are necessary to create a new strategy to treat these high-risk patients.     

Clinical efficacy of co-trimoxazole versus amoxicillin twice daily for treatment of pneumonia: a randomised controlled clinical trial in Pakistan

Aims: To compare the clinical efficacy of twice daily oral co-trimoxazole with twice daily oral amoxicillin for treatment of childhood pneumonia. Methods: Randomised controlled, double blind, multicentre study in outpatient departments of seven hospitals and in one community health service. A total of 1471 children (aged 2–59 months) with non-severe pneumonia were randomly assigned to 25 mg/kg amoxicillin (n = 730) or 4 mg/kg trimethoprim plus 20 mg/kg sulphamethoxazole (co-trimoxazole) (n = 741). Both medicines were given orally twice daily for five days. Results: Data from 1459 children were analysed: 725 were randomised to amoxicillin and 734 to co-trimoxazole. Treatment failure in the amoxicillin group was 16.1% compared to 18.9% in the co-trimoxazole group. Multivariate analysis showed that treatment failure was more likely in infants who had history of difficult breathing or those who had been ill for more than three days before presentation. Conclusions: Both amoxicillin and co-trimoxazole were equally effective in non-severe pneumonia. Good follow up of patients is essential to prevent worsening of illness.     

Hemolytic uremic syndrome and diarrhea associated with Escherichia coli O157:H7 in a day care center

Three cases of hemolytic uremic syndrome with bloody diarrhea occurred during an outbreak of diarrheal illness in children aged 4 months to 9 years who attended a day care center. Thirty-six (34%) of 107 had diarrhea (three or more loose or watery stools in 24 hours) lasting greater than or equal to 3 days. Thirty-one (48%) of 64 children younger than 4 years of age but only (12%) of 43 in the older classes became ill (relative risk 4.0, P less than 0.001). Eleven (31%) of the 36 children with diarrhea had blood in their stools. Sequential movement of illness from class to class was consistent with person-to-person spread. Ten (18%) of 56 family members of ill children but only one of 45 family members of well children younger than 4 years of age developed a diarrheal illness (P less than 0.05). Escherichia coli O157:H7 was detected in two of eight stool specimens from children who had bloody diarrhea (one with hemolytic uremic syndrome), two of seven with nonbloody diarrhea, and none of nine who remained well. All three stool specimens obtained at less than or equal to 6 days compared with one of nine obtained at greater than 6 days after onset yielded this organism (P less than 0.02). E. coli O157:H7 can cause hemolytic uremic syndrome and both nonbloody and bloody diarrhea, and can spread within families and through modes other than foodborne transmission.     

Safety and immunogenicity of a three dose regimen of two tetravalent live-attenuated dengue vaccines in five- to twelve-year-old Thai children

OBJECTIVE: The safety and immunogenicity of tetravalent live-attenuated dengue vaccines after a three dose vaccination series were evaluated in Thai children. METHOD: One hundred three healthy flavivirus-seronegative schoolchildren ages 5 to 12 years were randomized to receive either dengue vaccine containing 3, 2, 1 and 2 log10 of the 50% cell culture infective dose, respectively, of the live-attenuated dengue vaccine serotypes 1, 2, 3 and 4 per dose (F3212; n = 40) or 3, 3, 1 and 3 log10 of the 50% cell culture infective dose (F3313; n = 42) or purified Vero cell rabies vaccine (control group; n = 21) given in a two dose schedule (3 to 5 months apart). A third dose was administered 8 to 12 months after the second dose to 90 subjects. Safety and immunogenicity were evaluated within 28 days after each injection. RESULTS: No serious adverse event related to the vaccines occurred. Most children experienced mild to moderate fever, rash, headache and myalgia occurring within 12 days after Dose 1 and generally lasting 3 days or less. One subject in Group F3212 had a 1-week dengue-like fever. Reactogenicity was minimal after Doses 2 and 3. Transient mild variations in liver enzymes and hematologic indices were noted mainly after Dose 1. After the third dose 89% of the subjects in Group F3212 seroconverted (neutralizing antibody response, > or =10) to all four serotypes, and all children in Group F3313 seroconverted. CONCLUSION: This study demonstrates a moderate although improvable reactogenicity and high seroconversion rates against the four serotypes of dengue after a three dose schedule of tetravalent live-attenuated dengue vaccine in children.     

Effectiveness of an herbal preparation containing echinacea, propolis, and vitamin C in preventing respiratory tract infections in children: a randomized, double-blind, placebo-controlled, multicenter study

OBJECTIVE: To evaluate the effectiveness and safety of a preparation containing echinacea, propolis, and vitamin C in the prevention of respiratory tract infections in children during a 12-week winter period. DESIGN: Randomized, double-blind, placebo-controlled study. SUBJECTS: Four hundred thirty children, aged 1 to 5 years, were randomized to an herbal extract preparation (n = 215) or a placebo elixir (n = 215). INTERVENTION: Administration of an herbal preparation (Chizukit) containing 50 mg/mL of echinacea, 50 mg/mL of propolis, and 10 mg/mL of vitamin C, or placebo (5.0 mL and 7.5 mL twice daily for ages 1 to 3 years and 4 to 5 years, respectively) for 12 weeks. RESULTS: Significant mean +/- SD reductions of illnesses were seen in the Chizukit group in the number of illness episodes, 138 vs 308 (55% reduction); number of episodes per child, 0.9 +/- 1.1 vs 1.8 +/- 1.3 (50% reduction, P<.001); and number of days with fever per child, 2.1 +/- 2.9 vs 5.4 +/- 4.4) (62% reduction, P<.001). The total number of illness days and duration of individual episodes were also significantly lower in the Chizukit group. Adverse drug reactions were rare, mild, and transient. CONCLUSION: A preventive effect of a product containing echinacea, propolis, and vitamin C on the incidence of respiratory tract infections was observed.     

Randomized,double-blind,placebo-controlled trial of oral albuterol in infants with mild-to-moderate acute viral bronchiolitis

OBJECTIVE: To determine whether oral albuterol is effective in reducing symptomatology of acute viral bronchiolitis in infants with mild-to-moderate illness. STUDY DESIGN: In a randomized, double-blind trial, previously well infants were randomized upon discharge from the emergency department to receive either albuterol (0.1 mg/kg/dose) three times per day or placebo three times per day for 7 days. Daily standardized telephone interviews were conducted for as long as 14 days. The primary outcome was the time to resolution of illness. Secondary outcomes included time to normal feeding, normal sleeping, quiet breathing, resolved cough, and coryza. RESULTS: We studied 129 infants (albuterol, n = 64; placebo, n = 65). Baseline characteristics were similar between groups. The overall mean age was 5.3 months, 60% were male, and 49 of 61 tested infants were positive for respiratory syncytial virus. The median (95% confidence interval) time to resolution of illness (days) was similar: albuterol, 9.0 (8-13); placebo, 8.0 (7-9); P =.3) (log-rank test). There were no significant group differences in any secondary outcome. Health care revisit and admission rates were similar between groups. CONCLUSIONS: No significant group differences in either primary or secondary outcomes in infants treated with oral albuterol versus placebo were found. The widespread use of oral albuterol in this patient group is not recommended.     

A randomized study of tracking with outreach and provider prompting to improve immunization coverage and primary care

OBJECTIVE: To compare and measure the effects and cost-effectiveness of two interventions designed to raise immunization rates. SETTINGS: Nine primary care sites serving impoverished and middle-class children. SUBJECTS: Complete birth cohorts (ages 0 to 12 months; n = 3015) from these sites. INTERVENTIONS: Two 18-month duration interventions: 1) tracking with outreach [tracking/outreach] to bring underimmunized children to their primary care provider office, and 2) a primary care provider office policy change to identify and reduce missed immunization opportunities (prompting). DESIGN: Randomized, controlled trial, randomizing within sites using a two-by-two factorial design. Subjects were allocated to one of four study groups: control, prompting only, tracking/outreach only, and combined prompting with tracking/outreach. Outcomes were obtained by blinded chart abstraction. MEASURES: Immunization status for age; number of days of delay in immunization; primary care utilization; and rates of screening for occult disease. RESULTS: Out of 3015 subjects, 274 subjects (9%) transferred out of the participating sites or had incomplete charts and were excluded. The 2741 (91%) remaining subjects were assessed. At baseline, study groups did not differ in age, gender, insurance type, or immunization status. Of the remaining subjects, 63% received Medicaid. Final series-complete immunization coverage levels were: control, 74%; prompting-only, 76%; tracking/outreach-only 95%; and combined tracking/outreach with prompting, 95%. Analysis of variance showed that: 1) tracking/outreach increased immunization rates 20 percentage points; 2) tracking/outreach decreased mean immunization delay 63 days; 3) tracking/outreach increased mean health supervision visits 0.44 visits per child; 4) tracking/outreach increased mean anemia screening 0.17 screenings per child and mean lead screenings 0.12 screenings per child; 5) impact of tracking/outreach was greatest for uninsured and impoverished patients; and 6) the prompting intervention had no impact on the studied outcomes, and its failure was caused by inconsistent use of prompts and failure to vaccinate ill children when prompted. Using tracking/outreach, the cost per additional child fully immunized was $474. Each $1000 spent on the tracking/outreach intervention resulted in: 2.1 additional fully vaccinated children and 668 fewer child-days of delayed immunization; 4.6 additional health supervision visits and 5.9 additional other visits to the primary care provider; and 1.8 additional anemia screenings and 1.3 additional lead screenings. CONCLUSIONS: Outreach directed toward children not up-to-date on immunizations improves not only immunization status, but also health supervision visit attendance and screening rates. The cost per additional child immunized was high, but should be interpreted in view of the spillover benefits that accompanied improved immunization. Effective means to improve coverage by reducing missed immunization opportunities still need to be identified.     

Utility of liver biopsy culture in pediatric liver transplant recipients

Abstract: The purpose of our study was to determine the utility of the practice of culturing percutaneous liver biopsy specimens obtained from pediatric LT recipients for evaluation of fever and/or elevated serum aminotransferases. Accordingly, a retrospective analysis was done of the 101 liver biopsies obtained during an eight-year period which had been submitted for bacterial, fungal and/or viral culture (out of a total of 174 biopsies in 38 patients). The purpose of the analysis was to ask three questions. (1) What organisms were cultured? (2) Were there clinical profiles that were characteristic of the type of organism? (3) Was the practice cost-effective? The analysis indicated that 34/86 biopsy cultures were positive for bacteria, 4/75 for fungus and 2/81 for virus. Clinical and laboratory data for children with cultures positive for enteric flora (n = 9) were compared to those with cultures positive for Gram-positive organisms (n = 17), laboratory contaminants (n = 8), and those with negative cultures (n = 52). Children with biopsies positive for enteric flora had a ‘cholestatic profile’: mean direct bilirubin 7 mg/dl, ALT 78 IU/l, direct bilirubin/ALT 0.09, in comparison to children with biopsies positive for Gram-positive flora. These children had a ‘hepatocellular profile’: mean direct bilirubin 4 mg/dl, ALT 332 IU/l, direct bilirubin/ALT 0.01 (p = 0.04 versus the enteric flora values) and a high percentage of polymorphonuclear leukocytes (mean 69% versus 38% for those with negative cultures, p = 0.001.) The charge for performing each bacterial culture was $28 (total $28 × 86 = $2408: $268 per enteric flora-positive biopsy; $93 per biopsy positive for either enteric flora or Gram-positive flora). The charge for each fungal culture was also $28 (total $28 × 75 = $2100: $525 per positive culture), while the cost for each viral culture was $140 (total $140 × 81 = $11 340: $5670 per positive culture). Thus, discounting the eight cultures positive for laboratory contaminants, a total of $15 848 was spent for 32 positive cultures. Given the high cost of liver transplantation, this information suggests that discretion should be used in submission of liver biopsy samples for culture in pediatric transplant patients. We recommend that when liver biopsies are performed for evaluation of elevated serum aminotransferases and/or fever, culture of biopsy specimens for bacteria should be considered in children with a ‘cholestatic profile’: direct bilirubin ≥ 7 mg/dl and direct bilirubin/ALT > 0.08, or a ‘hepatocellular profile’: direct bilirubin ≤ 4 mg/dl and direct bilirubin/ALT < 0.05, together with polymorphonuclear leukocytes > 70%. Following these guidelines might provide valuable information pertinent to patient management (especially since Gram-negative organisms can sometimes be cultured from the liver and not from blood) while reducing costs. Fungal cultures should be restricted to critically ill children. However, our data suggest that the practice of obtaining fungal and viral cultures of the liver in most pediatric transplant patients has an unacceptably high cost/benefit ratio, particularly since recovery of the organism from the peripheral blood is likely.     

Human monocytic ehrlichiosis in children

BACKGROUND: Human monocytic ehrlichiosis (HME) is a tick-borne illness caused by Ehrlichia chaffeensis. Data about disease in children have been largely derived from case reports or small case series. METHODS: A retrospective review of all medical and laboratory records from 6 sites located in the "tick belt" of the Southeastern United States was carried out. Demographic, history and laboratory data were abstracted from the identified medical records of patients. Bivariate statistical comparisons were performed using Fisher exact test or Wilcoxon rank sum tests. RESULTS: Common clinical signs and symptoms of patients with HME (n = 32) included fever (100%), headache (69%), myalgia (69%), rash (66%), nausea/vomiting (56%), altered mental status (50%) and lymphadenopathy (47%). Only 48% had a complaint of fever, headache and rash. Common laboratory abnormalities included thrombocytopenia (94%), elevated aspartate aminotransferase (90%), elevated alanine aminotransferase (74%), hypoalbuminemia (65%), lymphopenia (57%), leukopenia (56%) and hyponatremia (55%). The median number of days of illness before the initiation of antirickettsial therapy was 6. Patients who received sulfonamides before starting doxycycline therapy developed a rash, were admitted to the hospital, and started doxycycline at a later date. Twenty-two percent of patients were admitted to the intensive care unit with 12.5% of patients requiring ventilatory and blood pressure support. CONCLUSIONS: Although HME has been recognized among children for almost 20 years, there is only a limited knowledge about its clinical course. Even among physicians practicing in endemic regions, few cases are diagnosed each year. More work is needed to understand the true burden of disease and the natural history among asymptomatically and symptomatically infected children.     

Variables influencing penicillin treatment outcome in streptococcal tonsillopharyngitis.

OBJECTIVE: To examine whether penicillin treatment success for group A beta-hemolytic streptococcal tonsillopharyngitis is influenced by patient age, number of days ill prior to initiation of treatment, number of prior episodes, season, total dosage (milligrams per kilogram), and frequency of administration (2 vs 3 times daily). METHODS: Four hundred seventy-eight children, adolescents, and young adults aged 2 to 21 years with acute symptoms compatible with the clinical diagnosis of group A beta-hemolytic streptococcal tonsillopharyngitis and a positive streptococcus rapid antigen detection test result were enrolled (intent-to-treat group). Patients were randomly assigned to receive penicillin V potassium, 250 mg 3 times daily (n = 239) or 500 mg 2 times daily (n = 239). Randomization was independent of patient body weight and treatment was for 10 days with both regimens. Follow-up examinations occurred, and cultures were obtained at 14 to 21 days after the initiation of antibiotic therapy; those with group A beta-hemolytic streptococcus isolated from a throat culture and who returned for follow-up were assessed for outcome (n = 359). RESULTS: Using a logistic regression analysis with a stepwise variable selection, we found the major variables associated with penicillin treatment success to be the number of days ill prior to initiation of treatment (P = .001; odds ratio, 1.55 [95% confidence interval, 1.2-2.1]) and the age of the child when infected (P = .004; odds ratio, 1.14 [95% confidence interval, 1.05-1.25]). The number of prior episodes within the preceding year, the season, the total daily penicillin dose (range, 8-76 mg/kg), and 2 vs 3 times daily dosing did not significantly alter treatment outcome. CONCLUSION: Treatment after 2 days of illness and of adolescent patients increases penicillin treatment success for group A beta-hemolytic streptococcal tonsillopharyngitis.     

Controlled trial of acyclovir for chickenpox evaluating time of initiation and duration of therapy and viral resistance

BACKGROUND: Chickenpox is prevalent in the US despite the availability of an effective vaccine. Acyclovir treatment is limited by concerns about efficacy if given after the first day of rash and by concerns about induction of viral resistance. OBJECTIVE: Evaluate initiation and duration of acyclovir treatment of chickenpox and its effect on viral resistance. STUDY DESIGN: Randomized, placebo-controlled, double blind trial in immunocompetent patients who were stratified by age at enrollment (children, 2 to 11 years; adolescents, > or = 12 to 18 years; adults, > or = 19 years) and duration of rash (< or = 24 h vs. >24 to 48 h). Lesions were staged, counted and cultured; temperatures and symptoms were recorded daily. INTERVENTION: Subjects presenting within 24 h of rash onset (Group A) were randomly assigned to 5 or 7 days of oral acyclovir treatment, 80 mg/kg/day up to a maximum of 3,200 mg/day in four divided doses. Subjects whose rash was >24 to 48 h old were randomized to receive 5 days of acyclovir treatment beginning on the first (Group B1) or second study day (Group B2). Matching placebos were used to ensure that subjects uniformly received 28 doses of study compound. RESULTS: Of the 177 subjects recruited Group A patients who were treated on the first day of rash had the greatest number of significantly shortened event times with 5 days of therapy being equivalent to 7 days. There also were some shorter times to events for Group B1 patients who began therapy on the second day of rash vs. Group B2 patients who started acyclovir on the third. These included: time to maximum lesion formation (adolescents, P = 0.007; children, P = 0.03); 50% healing in adolescents (P = 0.005); and residual facial lesions in adults (P = 0.047). The probability of viral shedding was significantly reduced for Group A subjects vs. Group B1 subjects (P = 0.006). Viruses shed during therapy remained susceptible to acyclovir and retained normal thymidine kinase function. CONCLUSIONS: Immunocompetent children, adolescents and adults with chickenpox displayed a gradation in their clinical responses to acyclovir that correlated with the time from onset of rash to initiation of therapy. Five days of therapy is sufficient because a 7-day course provided no additional benefit. The susceptibility to acyclovir of viruses shed during treatment did not change; however, the effect of therapy on resistance of latent virus was not assessed.